JPWO2019200007A5

JPWO2019200007A5 -

Info

Publication number: JPWO2019200007A5
Application number: JP2020555033A
Authority: JP
Publication date: 2022-04-18
Anticipated expiration: 2039-04-10

Claims

(A) (i) a ) Variable heavy chain CDR1 containing an amino acid sequence different from the amino acid sequence of SEQ ID NO: 42, or SEQ ID NO: 52, or SEQ ID NO: 62 by 3, 2, 1 or 0 or less amino acid residues, or b) Variable heavy chain CDR2 containing an amino acid sequence different from the amino acid sequence of SEQ ID NO: 43, or SEQ ID NO: 53, or SEQ ID NO: 63 by 3, 2, 1 or 0 or less amino acid residues, or c) SEQ ID NO: 44, Alternatively, a variable heavy chain CDR3 containing an amino acid sequence different from the amino acid sequence of SEQ ID NO: 54 or SEQ ID NO: 64 by 3, 2, 1 or 0 or less amino acid residues, or d) SEQ ID NO: 47, or SEQ ID NO: 57, or Variable light chain CDR1 containing an amino acid sequence different from the amino acid sequence of SEQ ID NO: 67 by 3, 2, 1 or 0 or less amino acid residues, or e) Amino acid sequence of SEQ ID NO: 48, or SEQ ID NO: 58, or SEQ ID NO: 68. And 3, 2, 1 or a variable light chain CDR2 containing an amino acid sequence different by 0 or less amino acid residues, or f) the amino acid sequence of SEQ ID NO: 49, or SEQ ID NO: 59, or SEQ ID NO: 69 and 3, 2, 1 Alternatively, a variable light chain CDR3 containing an amino acid sequence different by 0 or less amino acid residues, or
g) Variable heavy chain that differs from the variable heavy chain sequence of SEQ ID NO: 41 , SEQ ID NO: 51 or SEQ ID NO: 61 by 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less residues. Array or
h) Variable light chain different from the variable light chain sequence of SEQ ID NO: 46 , SEQ ID NO: 56 or SEQ ID NO: 66 by 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less residues. Array or
(Ii) (a) VH region of SEQ ID NO: 41 and VL region of SEQ ID NO: 46
(B) VH region of SEQ ID NO: 51 and VL region of SEQ ID NO: 56
(C) VH region of SEQ ID NO: 61 and VL region of SEQ ID NO: 66
At least one of
An antigen-binding molecule that specifically binds to PLL3, comprising, or comprising a sequence having at least 90% identity or at least 95% identity to said sequence.
Here, the VH region and the VL region are linked by at least one linker.
as well as
(B) CD28, CD8, OX-40, 4-1BB / CD137, CD2, CD7, CD27, CD30, CD40, Program Death-1 (PD-1), Inducible T Cell Costimulator (ICOS), Lymphatic Sphere function-related antigen-1 (LFA-1 (CDl la / CD18), CD3 gamma, CD3 delta, CD3 epsilon, CD247, CD276 (B7-H3), LIGHT, (TNFSF14), NKG2C, Igalpha (CD79a), DAP -10, Fc gamma receptor, MHC class I molecule, TNF receptor protein, immunoglobulin protein, cytokine receptor, integulin, signaling lymphocyte activation molecule (SLAM protein), activated NK cell receptor, BTLA, Doll Ligand receptor, ICAM-1, B7-H3, CDS , GITR, BAFFR, LIGHT, HVEM (LIGHT), KIRDS2, SLAMF7, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD19, CD4, CD8 alpha, CD8 beta , IL-2R Beta, IL-2R Gamma, IL-7R Alpha, ITGA4, VLA1, CD49a , IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CDl ld, ITGAE, CD103, ITGAL, CDl la , I TGAM, CDl lb, ITGAX, CDl lc, ITGBl, CD29, ITGB2, CD18 , ITGB7, NKG2D, TNFR2, TRANCE / RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tac) CRT AM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Lyl08), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162) ), LTBR, LAT, GADS, SLP-76, PAG / Cbp, CD19a, a ligand that specifically binds to CD83, or at least one co-stimulation domain that is the signaling region of any combination thereof, herein. , The CD28 co-stimulation domain is SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6 or SEQ ID NO: 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less amino acid residues. Number 8 distribution The CD8 co-stimulation domain contains a sequence different from the sequence, and the CD8 co-stimulation domain is the sequence of SEQ ID NO: 14 at 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less amino acid residues. The CD8 co-stimulation domain contains a different sequence and is different from the sequence of SEQ ID NO: 16 in 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less amino acid residues. Co-stimulation domain , including
Chimeric antigen receptors , including .

The chimeric antigen receptor according to claim 1, further comprising at least one activation domain.

The activation domain comprises CD3 , wherein the CD3 differs from the sequence of SEQ ID NO: 10 in 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less amino acid residues. The chimeric antigen receptor according to claim 2 , which comprises a CD3 zeta .

The co-stimulation domain contains a sequence different from the sequence of SEQ ID NO: 2 at 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less amino acid residues, and the activation domain is. The chimeric antigen receptor according to claim 1, which comprises a sequence different from the sequence of SEQ ID NO: 10 in 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 or 0 or less amino acid residues.

The polynucleotide encoding the chimeric antigen receptor according to claim 1.

A vector comprising the polynucleotide according to claim 5, which is a retrovirus vector, a DNA vector, a plasmid, an RNA vector, an adenovirus vector, an adenovirus-associated vector, a lentivirus vector, or any combination thereof.

An immune cell comprising the vector according to claim 6, which is a T cell, tumor infiltrating lymphocyte (TIL), NK cell, TCR expressing cell, dendritic cell or NK-T cell.

The immune cell according to claim 7, which is an allogeneic T cell.

The immune cell according to claim 7, which is an autologous T cell.

The immune cell according to claim 9, wherein the vector is introduced into a cell isolated from the patient's body or a cell proliferated from a sample taken from the patient's body.

The pharmaceutical composition comprising the immune cell according to claim 8.

The chimeric antigen receptor according to claim 1, wherein the linker comprises a scFv G4S linker or a scFv Whiterow linker.

A pharmaceutical composition comprising the chimeric antigen receptor according to claim 1, the cell according to claim 7, or the immune cell according to claim 8 for treating a disease or disorder in a subject in need of treatment. The pharmaceutical composition, wherein the disease or disorder is cancer.

Cancers include adrenal, liver, kidney, bladder, breast, stomach, ovary, cervix, uterus, esophagus, colonic rectum, prostate (eg, prostate adenocarcinoma), pancreas, lung (both small and non-small cells). ), Thyroid, carcinoma, sarcoma, glia blastoma, head and neck tumor, large cell neuroendocrine cancer (LCNEC), thyroid medullary cancer, glia blastoma, neuroendocrine prostate cancer (NEPC), high-grade gastrointestinal pancreas The pharmaceutical composition according to claim 13, which is cancer (GEP) and malignant melanoma.

The vector according to claim 6, wherein the vector is a lentiviral vector, and the lentiviral vector is a pGAR vector .